Carbon Dioxide → HCID 117821330, compound

HRID 59108Notes

Reaction equation

HRID 59108 reaction equation
CS([O:5][CH2:6][C:7]1[CH:12]=[C:11]([CH2:13][O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[N:10]=[C:9]([Cl:20])[N:8]=1)(=O)=O.[CH:21]1([CH2:24]O)[CH2:23][CH2:22]1.[OH-].[Na+].C(=O)=O>C1C=CC=CC=1.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.[Cl-].[Na+].O.O>[Cl:20][C:9]1[N:8]=[C:7]([CH2:6][O:5][CH2:24][CH:21]2[CH2:23][CH2:22]2)[CH:12]=[C:11]([CH2:13][O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[N:10]=1

Participants

9

Reactant 4

HCID 280Carbon DioxideHCID 14798Sodium HydroxideHCID 75644CyclopropanemethanolHCID 117821552HCID 117821552, compound

Product 1

HCID 117821330HCID 117821330, compound

Reagents, catalysts & solvents 4

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 241BenzeneSolventHCID 962WaterSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

(2-Chloro-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-4-yl)methyl methanesulfonate (0.47 g, 1.40 mmol) was dissolved in benzene (8 mL). Cyclopropylmethanol (0.222 mL, 2.81 mmol), 5 M sodium hydroxide (0.421 mL, 2.11 mmol) and tetrabutylammonium hydrogen sulfate (48 mg, 0.14 mmol) were added. The mixture was stirred vigorously at ambient temperature for 3 h. Solid carbon dioxide was added followed by brine and water. The mixture was extracted twice with ethyl acetate, the organic phase was separated and dried over sodium sulfate. The solution was concentrated in vacuum, and the residue was purified by column chromatography on silica eluting with a gradient of 0-50% of ethyl acetate in heptane. The solvents were evaporated and the residue was purified by preparative HPLC to give the title compound, 33 mg (7.5%).

Workup

  1. extractionThe mixture was extracted twice with ethyl acetate
  2. customthe organic phase was separated
  3. dry with materialdried over sodium sulfate
  4. concentrationThe solution was concentrated in vacuum
  5. customthe residue was purified by column chromatography on silica eluting with a gradient of 0-50% of ethyl acetate in heptane
  6. customThe solvents were evaporated
  7. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-2b1d3c4aafd148d5806d1554fc730be6
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

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